Patent DE-10339549-A1 (DE)
Title: New glucopyranosyloxy-pyrazole derivatives are sodium dependent glucose cotransporter inhibitors used for treating and preventing metabolic disorders, particularly diabetes
Inventor: HIMMELSBACH FRANK
IPC: A61K31/7056
Filed: 2003-08-26
Abstract: Glucopyranosyloxy-pyrazole derivatives (I), are new. Glucopyranosyloxy-pyrazole derivatives of formula (I), their tautomers, stereoisomers, mixtures and salts are new. [Image] R 1>pyrrolidin-3-yl, piperidin-3-yl or piperidin-4-yl (all optionally N-substituted by 1-4C alkyl, formyl, 1-4C alkylcarbonyl, 1-4C alkylsulfonyl, cyano, aminocarbonyl 1-4C alkylaminocarbonyl, di(1-4C alkyl)aminocarbonyl or 1-4C alkyloxycarbonyl), 3-6C alkynyl, tetrahydrofuran-3-yl, tetrahydropyran-3- or 4-yl, tetrahydrofuranyl(1-3C)alkyl or tetrahydropyranyl(1-3C)alkyl, or H, 1-6C alkyl, 1-4C alkyl substituted by 1-3 F, 2-4C alkyl substituted by one hydroxy or 1-3C alkoxy, or 3-6C alkenyl, 3-6C cycloalkyl, 3-6C cycloalkyl(1-3C)alkyl, aryl or aryl(1-3C)alkyl (when R 3> is R 3a>); R 2>1-4C alkyl (optionally substituted by 1-3 F) or 3-6C cycloalkyl; R 3>H, F, Cl, Br, I, 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl, 3-6C cycloalkyl, 3-6C cycloalkylidenemethyl, 1-6C alkoxy, 3-6C cycloalkoxy, 3-6C cycloalkyl(1-3C)alkyl, aryl, heteroaryl, aryl(1-3C)alkyl, heteroaryl(1-3C)alkyl, aryloxy, aryl(1-3C)alkoxy, methyl or methoxy (both substituted by 1-3 F), 2-4C alkyl or 2-4C alkoxy (both substituted by 1-5 F), 1-4C alkyl (substituted by CN, hydroxy or 1-3C alkoxy), CN, carboxy, 1-3C alkoxycarbonyl, aminocarbonyl (optionally substituted by 1 or 2 1-3C alkyl), pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1-ylcarbonyl, 4-(1-3C alkyl)-piperazin-1-ylcarbonyl, nitro, amino (optionally substituted by 1 or 2 1-3C alkyl), 1-4C alkylcarbonylamino, 1-4C alkylsulfonylamino, arylsulfonylamino, aryl(1-3C)alkylsulfonylamino, 1-4C alkylthio, 1-4C alkylsulfinyl, 1-4C alkylsulfonyl, arylthio, arylsulfinyl, arylsulfonyl or A; A : pyrrolidin-3-yloxy, piperidin-3-yloxy or piperidin-4-yloxy (all optionally N susbtituted by 1-4C alkyl, formyl, 1-4C alkylcarbonyl, 1-4C alkylsulfonyl, CN, aminocarbonyl (optionally substituted by 1 or 2 1-4C alkyl) or 1-4C alkoxycarbonyl), tetrahydrofuran-3-yloxy, tetrahydropyran-3-yl, tetrahydropyran-4-yloxy, tetrahydrofuranyl(1-3C)alkoxy or tetrahydropyranyl(1-3C)alkoxy; R 4>, R 5>H, F, Cl, Br, 1-3C alkyl, 1-3C alkoxy or methyl or methoxy (both substituted by 1-3 F), or adjacent CR 3> + CR 5>3-5C alkylene, methylenedioxy or difluoromethylenedioxy; R 3a>A, or R 3a> + R 4>difluoromethylenedioxy, 3-6C cycloalkoxy or 3-6C cycloalkylidene-methyl, where R 4> is not H; R 6>, R 7a>, R 7b>, R 7c>H, 1-18C alkylcarbonyl, 1-18C alkyloxycarbonyl, arylcarbonyl or aryl(1-3C alkyl)carbonyl; aryl : phenyl or naphthyl (both optionally substituted by 1 or 2 R h); R hF, Cl, Br, I, 1-3C alkyl, di- or tri-fluoromethyl, 1-3C alkoxy, di- or tri-fluoromethoxy or CN; heteroaryl : pyrrolyl, furanyl, thienyl or pyridyl (all with 1 or 2 methine optionally replaced by N), or indolyl, benzofuranyl, benzothienyl, quinolyl or isoquinolyl (all with 1-3 methine optionally replaced by N) (all optionally substituted by 1 or 2 R h). An independent claim is also included for the preparation of (I). ACTIVITY : Antidiabetic; Antiarteriosclerotic; Anorectic; Hypotensive; Cardiant; Antilipemic. Tests are described, but no results are given. MECHANISM OF ACTION : Sodium dependent glucose cotransporter (SGLT) inhibitor; SGLT2 inhibitor.